IP3r-1 Regulation and Egg Activation
IP3r-1 调节和卵激活
基本信息
- 批准号:7618191
- 负责人:
- 金额:$ 25.13万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-05-07 至 2012-04-30
- 项目状态:已结题
- 来源:
- 关键词:ActinsAddressAffectAntibodiesAssisted Reproductive TechnologyBiochemicalCalciumCell CycleCell Cycle StageConfocal MicroscopyConsensusCytoskeletonDevelopmentEmbryoEmbryonic DevelopmentEndoplasmic ReticulumEvaluationExperimental ModelsFertilizationGoalsHormonalHumanImageryImmunoblottingImmunofluorescence ImmunologicImmunoprecipitationIn VitroInositolInterphaseLaboratoriesLeadLigandsLocationMammalsMediatingMeiosisMessenger RNAMetaphaseMicrofilamentsMicroinjectionsMicrotubulesMitosisMitoticMolecularMonitorMusMutationOocytesOvulationPathway interactionsPatternPeriodicalsPhospholipasePhosphoproteinsPhosphorylationPhosphotransferasesProductionRegulationResearch PersonnelRoleSeriesSignal TransductionSiteSomatic CellStagingWorkagedegghuman PLK1 proteinimprovedkinase inhibitorligand gated channeloocyte maturationprogramsreceptorresponsesperm cellsuccesszygote
项目摘要
DESCRIPTION (provided by applicant): The long-term goal of this application is to elucidate the mechanisms that control egg activation in mammalian species. Mammalian eggs are ovulated arrested at the metaphase stage of the second meiosis (MIl). Egg activation entails exit from MIl and the completion of a series of morphological and biochemical changes that initiate the mitotic and, consequently, the developmental program. Fertilization induces egg activation by evoking periodical changes in the intracellular concentration of free calcium ([Ca2+]i) known as [Ca2+]i oscillations. The inositol 1, 4, 5-trisphosphate receptor (IP3R-1), a ligand-gated channel, mediates the [Ca2+]i rises at fertilization. Evidence shows that the mass, distribution and conductivity of IP3R-1 are regulated during maturation and fertilization and that this is required to establish the temporal and spatial organization of the [Ca2+]i responses at fertilization. Despite this pivotal role of IP3R-1, little is known about the molecular mechanisms that control its function in eggs. Here, we hypothesize that IP3R-1 constitutes a key regulatory locus for the organization of Ca2+ release during egg activation. To further elucidate the mechanisms that control IP3R-1 function we propose to: 1) investigate how IP3R-1 degradation is regulated during activation and how it impacts sperm-initiated [Ca2+]i oscillations; 2) determine whether IP3R-1 phosphorylation by cell cycle-associated kinases mediates the observed association between the cell cycle, IP3R-1 conductivity and [Ca2+]i oscillations; 3) examine the localization and mechanism(s) responsible for IP3R-1 redistribution and how IP3R-1 distribution/cortical cluster formation affects Ca2+ release. To address these questions we will perform [Ca2+]i monitoring, immunoblotting, immunofluorescence, microinjection of mRNAs, release of caged compounds, and mutations and tagging of IP3R-1 followed by expression in eggs/somatic cells and confocal microscopy visualization. Relevance: Given the diverse and precise regulation of IP3R-1 function during maturation, evaluation of these parameters after ovulation/maturation may provide markers with which to assess the impact of hormonal stimulation/in vitro maturation conditions on oocyte quality. Also, since abnormal Ca2+ release occurs in eggs aged after ovulation and this may lead to embryo fragmentation, elucidation of the mechanisms that control IP3R-1 function promises to improve embryo development and the success of Assisted Reproductive Technologies.
描述(由申请人提供):本申请的长期目标是阐明哺乳动物物种中控制卵激活的机制。哺乳动物卵在第二次减数分裂(MIl)的中期阶段停止排卵。卵激活需要从MIl退出并完成一系列形态学和生化变化,这些变化启动有丝分裂并因此启动发育程序。受精通过引起细胞内游离钙([Ca 2 +]i)浓度的周期性变化(称为[Ca 2 +]i振荡)来诱导卵活化。1,4,5-三磷酸肌醇受体(IP 3R-1)是一种配体门控通道,介导受精时[Ca 2 +]i的升高。有证据表明,IP 3R-1的质量,分布和电导率在成熟和受精过程中受到调节,这是建立受精时[Ca 2 +]i响应的时空组织所必需的。尽管IP 3R-1发挥着关键作用,但人们对控制其在卵子中功能的分子机制知之甚少。在这里,我们假设,IP 3R-1构成了一个关键的调控位点的组织在卵激活过程中的Ca 2+释放。为了进一步阐明IP 3R-1功能的调控机制,我们提出:1)研究IP 3R-1的降解在精子激活过程中是如何调节的,以及它是如何影响精子启动的[Ca ~(2+)]i振荡的; 2)确定细胞周期相关激酶对IP 3R-1的磷酸化是否介导了细胞周期、IP 3R-1电导率和[Ca ~(2+)]i振荡之间的联系; 3)研究IP 3R-1再分布的定位和机制以及IP 3R-1分布/皮质簇形成如何影响Ca 2+释放。为了解决这些问题,我们将进行[Ca 2 +]i监测,免疫印迹,免疫荧光,mRNA的显微注射,笼状化合物的释放,以及IP 3R-1的突变和标记,然后在卵/体细胞中表达和共聚焦显微镜可视化。相关性:考虑到成熟过程中IP 3R-1功能的多样性和精确调节,排卵/成熟后这些参数的评估可能提供评估激素刺激/体外成熟条件对卵母细胞质量影响的标志物。此外,由于异常的Ca 2+释放发生在排卵后老化的卵子中,这可能导致胚胎碎裂,因此控制IP 3R-1功能的机制的阐明有望改善胚胎发育和辅助生殖技术的成功。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Rafael Antonio Fissore其他文献
Rafael Antonio Fissore的其他文献
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{{ truncateString('Rafael Antonio Fissore', 18)}}的其他基金
Mammalian Fertilization: Identifying the second sperm factor that induces residual calcium oscillations and its contributions to egg activation
哺乳动物受精:识别诱导残留钙振荡的第二个精子因子及其对卵子激活的贡献
- 批准号:
10574938 - 财政年份:2022
- 资助金额:
$ 25.13万 - 项目类别:
Regulation of Ca2+ influx in mouse oocytes and eggs during maturation and fertilization to improve assisted reproductive technologies and modulate fertility
调节小鼠卵母细胞和卵在成熟和受精过程中的 Ca2 流入,以改进辅助生殖技术并调节生育力
- 批准号:
9766344 - 财政年份:2018
- 资助金额:
$ 25.13万 - 项目类别:
Regulation of Ca2+ influx in mouse oocytes and eggs during maturation and fertilization to improve assisted reproductive technologies and modulate fertility
调节小鼠卵母细胞和卵在成熟和受精过程中的 Ca2 流入,以改进辅助生殖技术并调节生育力
- 批准号:
10401470 - 财政年份:2018
- 资助金额:
$ 25.13万 - 项目类别:
Frontiers in Reproduction (FIR) Training Course
生殖前沿 (FIR) 培训课程
- 批准号:
10617172 - 财政年份:2014
- 资助金额:
$ 25.13万 - 项目类别:
Release and molecular composition of mammalian SFs
哺乳动物 SF 的释放和分子组成
- 批准号:
6687127 - 财政年份:2003
- 资助金额:
$ 25.13万 - 项目类别:
Release and molecular composition of mammalian SFs
哺乳动物 SF 的释放和分子组成
- 批准号:
6772484 - 财政年份:2003
- 资助金额:
$ 25.13万 - 项目类别:
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